Uterine intravascular adenomyomatosis: Clinicopathological features and literature review of a rare entity

Abstract

Background

Intravascular adenomyomatosis (IA), characterised by endometrial-type glands or stroma embedded within smooth muscle tissue inside myometrial vessels, is a rare variant within the spectrum of uterine intravenous leiomyomatosis (IVL).

Case report

A 45-year-old nulligravid woman presented with hypermenorrhoea and a large uterine mass radiologically interpreted as a degenerated fibroid. Histopathological examination of the hysterectomy specimen revealed a cellular leiomyoma with smooth muscle fibres and endometrial-type stroma within CD31-lined myometrial vessels, showing low mitotic activity and no atypia or necrosis. The postoperative course was uneventful, and the patient remained disease-free 12 months after surgery.

Discussion

Although IA is a benign lesion, intravascular growth may mimic malignancy both radiologically and histologically. A comprehensive review of the literature identified only 11 reported cases, most diagnosed postoperatively, all showing benign behaviour after complete excision. Awareness of this condition may prevent overtreatment and misclassification.

Resumen

Antecedentes

La adenomiomatosis intravascular (AI), caracterizada por glándulas o estroma de tipo endometrial incrustados en tejido muscular liso dentro de los vasos miometriales, es una variante rara dentro del espectro de la leiomiomatosis intravenosa uterina (LIU).

Caso clínico

Mujer nulígrávida de 45 años que consultó por hipermenorrea y una masa uterina de gran tamaño interpretada radiológicamente como un fibroma degenerado. El examen histopatológico de la pieza de histerectomía reveló un leiomioma celular con fibras de músculo liso y estroma de tipo endometrial dentro de vasos miometriales revestidos por CD31, con baja actividad mitótica y sin atipia ni necrosis. La evolución posoperatoria fue favorable y la paciente permanecía libre de enfermedad 12 meses después de la cirugía.

Discusión

Aunque la AI es una lesión benigna, su crecimiento intravascular puede simular malignidad tanto radiológica como histológicamente. Una revisión exhaustiva de la literatura identificó solo 11 casos publicados, la mayoría diagnosticados en el período posoperatorio, todos con comportamiento benigno tras la resección completa. El reconocimiento de esta entidad puede prevenir tratamientos excesivos y errores de clasificación.

Introduction

Uterine intravascular adenomyomatosis (IA), first reported by Clement in 1988,¹ is a benign gynaecological neoplasm that falls within the spectrum of intravenous leiomyomatosis (IVL). It is characterised by the presence of smooth muscle and endometrial-type glands or stroma within the myometrial vessels,² whose appearance may vary depending on the menstrual cycle and other individual conditions.

Although exceedingly rare, this entity is a clinically relevant diagnostic pitfall that can mimic adenomyosis or endometriosis with vascular involvement, as well as malignant tumours that exhibit vascular invasion, such as endometrial stromal sarcoma and leiomyosarcoma).³

Herein, we report the case of a 45-year-old woman with a clinical diagnosis of fibroids who underwent total hysterectomy, with histopathological assessment revealing IA. To highlight the clinical relevance of such findings, we reviewed published cases of uterine IA and summarised their main epidemiological and clinicopathological characteristics, including the most commonly used diagnostic methods and treatment options.

Case report

A 45-year-old nulligravid woman was referred by her primary care physician with hypermenorrhoea and a progressive increase in abdominal girth over the preceding year. She had no significant medical or surgical history, except for seven-day heavy menstrual periods with iron-deficiency anaemia, despite iron supplementation. Upon physical examination, a firm abdominopelvic mass extending up to the umbilicus was noted.

Abdominal and transrectal ultrasonography demonstrated a markedly enlarged uterus (214 mm × 145 mm × 113 mm) containing a solid-cystic intracavitary mass (type IV central Doppler pattern) measuring 126 mm × 129 mm × 100 mm (Fig. 1A). An endometrial biopsy was performed, yielding unremarkable results, and tumour markers were within normal ranges. Subsequently, an abdominopelvic computed tomography (CT) scan was obtained, revealing a large, solid, heterogeneous uterine mass, raising the differential diagnosis between a fibroid with areas of cystic degeneration and a malignant uterine neoplasm (e.g., leiomyosarcoma or endometrial stromal sarcoma) (Fig. 1B). Additional findings included marked varicose dilatation of both ovarian veins, minimal free fluid in the pouch of Douglas, and incidental millimetric hepatic lesions. Magnetic resonance imaging (MRI) characterised the liver lesions as simple cysts.

Fig. 1.

(A) Longitudinal abdominal ultrasonography section showing a uterine mass measuring 12.9 cm in its greatest diameter. (B) Contrast-enhanced computed tomography demonstrating a large, solid, heterogeneous uterine mass, suspicious for fibroid with cystic degeneration.

Total hysterectomy with bilateral salpingo-oophorectomy was performed by laparotomy, revealing a normal-appearing abdominal cavity with macroscopically unremarkable adnexa, a small amount of peritoneal fluid, and a 1450 g uterus, which was submitted for histopathological examination. Sections of the specimen demonstrated a myomatous mass occupying almost the entire uterine body, histologically composed of a cellular proliferation with a mitotic count of <1 mitosis/HPF, with no evidence of necrosis or cellular atypia, and a focus of adenomyosis in the uterine fundus. In addition, several smooth muscle cells and nests of endometrial-type stroma were identified within the vessels of the remaining myometrium (Fig. 2), confirming the diagnosis of uterine intravascular adenomyomatosis.

Fig. 2.

(A, B) Smooth muscle cells along with nests of endometrial-type stroma within a vessel adjacent to a leiomyoma. No necrosis or atypia is observed. (C, D) CD31 immunostaining highlights the endothelium of this vessel within the thickness of the spared myometrium. (E–H) Caldesmon (E, F) and CD10 (G, H) show strong positivity in smooth muscle cells and endometrial stroma, respectively.

The patient was discharged on the third postoperative day without complications or significant findings on imaging tests. Follow-up imaging demonstrated radiological stability, with no significant findings on CT 12 months after the procedure.

Discussion

This case highlights the challenges in the identification of uterine intravascular adenomyomatosis (IA). Under-recognition of this entity is likely driven by its nonspecific clinical and radiological features, as well as the focal histological involvement, which may be missed when sampling is limited. In addition, scant endometrioid-type glands or stroma within vascular spaces may be overlooked or misinterpreted as carryover adenomyosis.

Several hypotheses have been proposed to explain the origin of uterine adenomyosis, most of which are invoked when discussing IA. One of the most widely cited is the invasion theory, which postulates that endometrial tissue extends into the myometrium across the endometrial–myometrial interface by a pushing mechanism.⁴ Within this framework, the tissue injury and repair (TIAR) model suggests that chronic uterine hyperperistalsis produces microtrauma at the endomyometrial junction, activating repair cascades and local oestrogen-related signalling, thereby facilitating inward displacement of basal endometrium into the myometrium.⁴ This process may explain not only the presence of endometrial glands but also the hyperplastic response of the surrounding smooth muscle tissue. Another proposed mechanism is the metaplasia theory, which posits that uterine adenomyomatosis arises from metaplasia of displaced embryonic pluripotent Müllerian remnants or multipotent uterine cells (including perivascular cells), which differentiate into endometrial stromal cells and subsequently induce the formation of epithelial structures.⁵ Finally, the hormonal factor theory suggests that hormonal changes and increased oestrogen levels may contribute to the development of uterine adenomyomatosis,⁶ based on the frequent association of this lesion with endometriosis and other endocrine disorders.

To the best of our knowledge, only 11 cases have been reported in the literature^1,3,8–10 (Table 1). In these cases, patients ranged in age from 39 to 69 years, with a mean age of 47 years. Most cases were identified postoperatively in hysterectomy specimens performed for symptomatic uterine disease (e.g., hypermenorrhoea or chronic pelvic pain), reflecting the nonspecific clinical and radiological presentation of this lesion. Consequently, histopathological assessment remains the gold standard for diagnosis. Histologically, IA is characterised by endometrial-type glands or stroma intermingled with smooth muscle cells, showing little or no atypia and a low mitotic rate (<1/10 HPFs). Perivascular fibrosis and thickening of the surrounding myometrium may be observed, likely as a reactive inflammatory response to the aberrant endometrial tissue. Notably, concomitant uterine adenomyosis was reported in 75% of cases, and in 67% the adenomyotic foci were described as closely associated with the vessels involved in IA, supporting a potential biological link between both processes. Hysterectomy is generally associated with a complete therapeutic response, with no recurrence observed after months of follow-up. The only case of residual disease progression, reported by Fitzpatrick et al. (2022), involved extensive infiltration of the broad ligament at diagnosis and concomitant endometriosis in a rectal nodule.³ Given that IA falls within the spectrum of IVL, venous extension through the gonadal veins to the right heart cavities should be carefully excluded, as distant tumour dissemination may result in fatal complications such as pulmonary embolisms or severe obstruction of blood flow.⁷

Table 1.

Epidemiological and clinicopathological features of uterine intravascular adenomyomatosis (IA) reported in the literature.

Case	Age	Clinical presentation	Histological features of IA	Extrauterine extension	Adenomyosis foci	Surgery performed	Follow-up
1. Clement et al. (1988)^1	47	Stress incontinence, pelvic mass	Cellular smooth muscle; proliferative endometrium	No	Close	TH + BSO	Not available (recent case)
2. Hirschowitz et al. (2013)^8	69	Pelvic mass and prolapse	Fascicular smooth muscle with inactive endometrioid glands and stromal elements; scant mature adipose tissue	No	Close	TH	Not available (recent case)
3. Hirschowitz et al. (2013)^8	46	Hypermenorrhea	Fascicular, cytologically bland smooth muscle with benign endometrioid glands and stroma	IVL in a paratubal vessel	Far apart	TH + BSO	No recurrence11 years after
4. Hirschowitz et al. (2013)^8	50	Pelvic mass	Fascicular smooth muscle with occasional prominent vessels and benign inactive endometrioid tissue	Vasculitis in cervix and myometrium	Close	TH + BSO	No recurrence6 wk after
5. Hirschowitz et al. (2013)^8	41	Pelvic mass	Fascicular smooth muscle with thick-walled vessels and focal bizarre (symplastic) changes	No	Close	TH + BS.BO 4 mo later	No recurrence 8 months later
6. Hirschowitz et al. (2013)^8	45	Pelvic mass	Fascicular smooth muscle with occasional thick-walled vessels and occasional cystic inactive endometrial stroma	No	Close	TH + BSO	No recurrence 2 years later
7. Cosan et al. (2017)^9	49	Dysmenorrhea, hypermenorrhea	Lobulated structures of cytologically bland smooth muscle with inactive endometroid glands and stroma	No	Close	TH + BSO	No recurrence 3 years later
8. Maghsoudi et al. (2019)^10	48	Hypermenorrhea, pelvic mass	Typical endometrial stroma with hypertrophied smooth muscle	No	Close	Subtotal hysterectomy	No recurrence 6 months after
9. Fitzpatrick et al. (2022)^3	42	Dysmenorrhea	Plexiform/pseudoepithelioid smooth muscle with endometrial-type glands and stroma	Broad-ligament infiltration and presence of endometriosis in a rectal nodule	Not specified	TH	Progression of residual disease (1 y); stable disease burden at 7 y
10. Fitzpatrick et al. (2022)^3	43	Pelvic mass	Plexiform smooth muscle with prominent hydropic change and endometrial-type glands/stroma endometrial	Endometriosis in cervix, serosa, and left ovary	Not specified	TH + LSO + RS	No recurrence2 years after
11. Fitzpatrick et al. (2022)^3	39	Dysmenorrhea, pelvic mass	Endometrial glands and stroma surrounded by a smooth muscle cuff	Extension of IVL and IA to right adnexal soft tissue: endometriosis in left fallopian tube, parametrium, and uterine serosa	Not specified	TH + RSO + LS	No recurrence5 months after
12. Our case	45	Hypermenorrhea and pelvic mass	Typical endometrial stroma with cellular smooth muscle	No	Close	TH + BSO	No recurrence12 months after

Abbreviations: IA, intravascular adenomyomatosis; IVL, intravascular leiomyomatosis; TH, total hysterectomy; BSO, bilateral salpingo-oophorectomy; BS, bilateral salpingectomy; BO, bilateral oophorectomy; LSO, left salpingo-oophorectomy; RSO, right salpingo-oophorectomy; LS, left salpingectomy; RS, right salpingectomy.

Conclusion

Uterine IA is a rare and under-recognised entity within the spectrum of IVL that presents significant diagnostic challenges due to its nonspecific clinical presentation and imaging features, which may overlap with other uterine neoplasms exhibiting vascular involvement. Comprehensive histopathological assessment is essential for accurate diagnosis and appropriate management. Reported cases indicate an overall benign course following complete excision; however, the possibility of extrauterine extension warrants careful postoperative surveillance.

Authorship

All authors had access to the data and contributed to the writing of this manuscript.

Ethics

Written informed consent was obtained from the patient.

Funding

No specific funding was received from any public, commercial or not-for-profit organisations for the work described in this article.

Conflict of interest

The authors declare that they have no competing interests.

Data availability statement

All data relevant to this study are included in this published article.